The purpose of this study was to compare bone reconstruction using either mesenchymal stem cells (MSCs) or total bone marrow (TBM) in association with biphasic calcium phosphate (BCP) granules after irradiation in a rat model. Three weeks after an external irradiation of the hind limbs of rats, four bone defects were created per animal. The defects were filled with either BCP alone, or with a mixture of BCP and TBM, or with a mixture of BCP and MSCs (adipose-derived or bone marrow-derived MSCs). Three weeks after implantations, new-bone formation was assessed. Histological examination showed osteoconductive and osteointegrative properties of BCP in irradiated tissue. The BCP-TBM mixture significantly improved bone ingrowth (p<0.05). The BCP-MSCs mixtures did not provide new-bone formation over and above that induced by BCP alone. This gives grounds for suspecting that there is a link between this result and the cellular and vascular weakness observed in irradiated bone. The BCP-TBM mixture may have induced an increased vascularization of irradiated bone. This could be due to the presence of all components in TBM that were lacking in the BCP-MSCs mixtures. BCP associated with TBM appears to be the most efficient material for bone substitution in irradiated areas.